The Cancer/Testis Antigen (CTA), Prostate-associated Gene 4 (PAGE4), is a stress-response protein that is upregulated in prostate cancer (PCa) especially in precursor lesions that result from inflammatory stress. In cells under stress, translocation of PAGE4 to mitochondria increases while production of reactive oxygen species decreases. Furthermore, PAGE4 is also upregulated in human fetal prostate, underscoring its potential role in development. However, the proteins that interact with PAGE4 and the mechanisms underlying its pleiotropic functions in prostatic development and disease remain unknown. Here, we identified c-Jun as a PAGE4 interacting partner. We show that both PAGE4 and c-Jun are overexpressed in the human fetal prostate; and in cell-based assays, PAGE4 robustly potentiates c-Jun transactivation. Single-molecule Förster resonance energy transfer experiments indicate that upon binding to c-Jun, PAGE4 undergoes conformational changes. However, no interaction is observed in presence of BSA or unilamellar vesicles containing the mitochondrial inner membrane diphosphatidylglycerol lipid marker cardiolipin. Together, our data indicate that PAGE4 specifically interacts with c-Jun and that, conformational dynamics may account for its observed pleiotropic functions. To our knowledge, this is the first report demonstrating crosstalk between a CTA and a proto-oncogene. Disrupting PAGE4/c-Jun interactions using small molecules may represent a novel therapeutic strategy for PCa.

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Background: The use of a rubber dam is more important than ever in today's COVID-19 era to limit cross infections. In children, the placement of the metal clamp to retain the rubber dam is perceived to be painful and often requiring a local anesthetic injection. This dissuades many clinicians from placing the rubber dam. Hence, this study evaluated the pain response of children to a SoftClamp™ compared to the conventional metal clamp. Materials and Methods: This was a randomized controlled, equal allocation ratio, split-mouth clinical trial. Forty-two children aged between 8 and 12 years, having two permanent mandibular molars in need of sealants, were divided into Groups A and B (metal clamp and SoftClamp™, respectively). The pain response was recorded using both an objective and a subjective scale i.e., the Faces Legs Activity Cry Consolability (FLACC) scale and the Wong Baker Faces Pain Rating Scale (WBFPRS). The level of significance was set at 5% (P < 0.05). The pain response recorded from the WBFPRS and the FLACC scale for the metal and the SoftClamp™ were analyzed using the Wilcoxon signed rank test. The difference in pain response between genders and between two age groups (below and above 10 years of age) was analyzed using the Mann–Whitney U-test. Results: The children reported mild discomfort to clamp placement in both the scales. The P values for the FLACC and WBFPRS scores comparing the pain response to the metal and SoftClamp™ were 0.311 and 0.149, respectively. Conclusion: There was no significant difference in the pain response of children to both the clamps. Good rubber dam application practices in children through the use of behavior guidance and a proper topical anesthesia technique may play a far more important role regardless of the clamp used. But the SoftClamp™, with its more child friendly appearance could be a viable alternative to the metal clamp in children.